In the period for which funding is sought, I plan to study the role of extracellular matrix (ECM) in embryonic induction of craniofacial tissues. This work includes an extensive ultrastructural analysis of embryonic placode formation, comparing the development of optic, otic, and nasal anlage by scanning and transmission electron microscopy. The extracellular matrix components associated with the development of these placodes will be biochemically characterized and the relation of surface components to intracellular organelles clarified. Using the interaction between the lens epithelium and neural retina as a model system, the influence of the lens placode-neural epithelium ECM interface on the establishment and maintenance of placode morphology will be studied in vitro. Likewise, the influence of the ECM interface on subsequent invagination of the lens analage will be evaluated. In addition, I will analyze the role of the lens anlage interface ECM on the production lens fibers and proteins by the invaginated lens epithelium. Other relatively undifferentiated embryonic epithelia will be challenged with lens-neural epithelium interface ECM to produce a placode, invaginate, and/or synthesize lens fibers. Experiments on the otic and nasal placodes will be designed using this basic information derived from study of lens induction. Finally, I will extend our recent studies on the role of ECM in the development of the cornea. Corneal epithelium of earlier stages than heretofore employed will be combined in vitro with lens or eye cup to determine the extent to which these tissues and their ECM influence the presumptive corneal epithelium to begin producing a primary stroma. The degreee to which other relatively uncommitted epithelia can respond to corneal "inductors" will also be assessed by tissue combination in vitro. Clarification of the role of ECM in embryonic tissue interaction will provide information leading to our understanding of normal and abnormal development of craniofacial structures.